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1 References American College of Gastroenterology Task Force on Irritable Bowel Syndrome, Brandt LJ, Chey WD, et al. An evidence- based position statement on the management of irritable bowel syndrome. Am J Gastroenterol. 2009;104(Suppl 1):S1-35. AMITIZA [package insert]. Bethesda, MD: Takeda Pharmaceuticals America., Inc; Takeda Pharmaceuticals America, Inc. Data on File. Azpiroz F, Bouin M, Camilleri M, et al. Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroentol Motil. 2007;19(Suppl 1): Bäckhed F, Ley JL, Sonnenburg DA, Peterson W, Gordon JI. Host- bacterial mutualism in the human intestine. Science. 2005;307(5717): Ballou SK, Keefer L. Multicultural considerations in the diagnosis and management of irritable bowel syndrome: a selective summary. Eur J Gastroenterol Hepatol. 2013;25(10): Barish CF, Drossman D, Johanson JF, Ueno R. Efficacy and safety of lubiprostone in patients with chronic constipation. Dig Dis Sci. 2010;55(4): Biesiekierski JR, Newnhham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double blind randomized placebo controlled trial. Am J Gastroenterol. 2011;106(3): Bijkerk CJ, de Wit NJ, Stalman WA, Knottnerus JA, Hoes AW, Muris JW. Irritable bowel syndrome in primary care: the patients and doctors views on symptoms, etiology and management. Can J Gastroenterol. 2003;17(6): Blackshaw LA, Brookes SJ, Grundy D, Schemann M. Sensory transmission in the gastrointestinal tract. Neurogastroenterol Motil. 2007;19(Suppl 1):1-19. Bracco A, Kahler K. Burden of chronic constipation must include estimates of work productivity and activity impairment in addition to traditional healthcare utilization. Am J Gastroenterol. 2004;99(suppl 10):S233. Abstract 719. Brandt LJ, Bjorkman D, Fennerty MB, et al. Systematic review on the management of irritable bowel syndrome in North America. Am J Gastroenterol. 2002;97(11 Suppl):S7- S26. Brandt LJ, Prather CM, Quigley EM, Schiller LR, Schoenfeld P, Talley NJ. Systematic review on the management of chronic constipation in North America. Am J Gastroenterol. 2005;100(Suppl 1):S5- S21.

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3 Drossman DA, Morris CB, Schneck S, et al. International survey of patients with IBS: symptom features and their severity, health status, treatments, and risk taking to achieve clinical benefit. J Clin Gastroenterol. 2009;43(6): Faigel DO. A clinical approach to constipation. Clin Cornerstone. 2002;4(4): Ford AC, Talley NJ, Spiegel BM, et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta- analysis. BMJ. 2008;337:a2313. Guilarte M, Santos J, de Torres I, Alonso C, et al. Diarrhea- predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut. 2007;56(2): Halpert, A. Dalton CB, Palsson O, et al. What patients know about irritable bowel syndrome (IBS) and what they would like to know. National Survey on Patient Educational Needs in IBS and development and validation of the Patient Educational Needs Questionnaire (PEQ). Am J Gastroenterol. 2007;102(9): Hulisz D. The burden of illness of irritable bowel syndrome: current challenges and hope for the future. J Managed Care Pharm. 2004;10(4): International Foundation for Functional Gastrointestinal Disorders (IFFGD). IBS Patients: Their Illness Experience and Unmet Needs Jailwala J, Imperiale TF, Kroenke K. Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials. Ann Intern Med. 2000;133(2): Johanson JF. Review of the treatment options for chronic constipation. MedGenMed. 2007;9(2):25. Johanson JF, Morton D, Geenen J, Ueno R. Multicenter, 4- week, double- blind, randomized, placebo- controlled trial of lubiprostone, a locally- acting type- 2 chloride channel activator, in patients with chronic constipation. Am J Gastroenterol. 2008;103(1): Kassinen A, Krogius- Kurikka L, Makivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differ significantly from that of healthy subjects. Gastroenterology. 2007;133(1): Kellow JE, Azpiroz F, Delvaux M, et al. Applied principles of neurogastroenterology: physiology/motility- sensation. Gastroenterology. 2006; 130(5): Knowles CH, Martin JE. Slow transit constipation as a model of human gut dysmotility. Neurogastroenterol Motil. 2000; 12(2):

4 Lacy BE, Rosemore J, Robertson D, Corbin DA, Grau M, Crowell MD. Physicians attitudes and practices in the evaluation and treatment of irritable bowel syndrome. Scand J Gastroenterol. 2006;41: Lee H, Park JH, Park DI, et al. Mucosal mast cell count is associated with intestinal permeability in patients with diarrhea predominant irritable bowel syndrome. J Neurogastroenterol Motil. 2013;19(2): Lembo A, Camilleri M. Chronic constipation. N Engl J Med. 2003;349(14): Lembo A, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011;365(6): Locke GR 3 rd, Pemberton JH, Phillips SF. American Gastroenterological Association Medical Position Statement: guidelines on constipation. Gastroenterology. 2000;119(6): Locke GR 3 rd, Zinsmeister AR, Talley NJ, Fett SL, Melton LJ. Risk factors for irritable bowel syndrome: role of analgesics and food sensitivities. Am J Gastroenterol. 2000;95(1): Longstreth GF, Wilson A, Knight K, et al. Irritable bowel syndrome, health care use, and costs: a U.S. managed care perspective. Am J Gastroenterol. 2003;98(3): Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5): Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. In: Drossman DA, Carrazziari E, Delvaux M, eds. Rome III: The Functional Gastrointestinal Disorders. McLean, VA: Degnon Associates; 2006: Mabeck CE, Olesen F. Metaphorically transmitted diseases. How do patients embody medical explanations? Fam Pract. 1997;14(4): Martin BC, et al. The annual cost of constipation in the U.S. ambulatory and inpatient settings. Gastroenterology. 2005;128 (suppl 2):A Abstract M974. McCormick JB, Hammer RR, Farrell RM, et al. Experiences of patients with gastrointestinal conditions: in their own words. Health Qual Life Outcomes. 2012;10:25. Published online Mar 8, Mearin F, Balboa A, Badía X, et al. Irritable bowel syndrome subtypes according to bowel habit: revisiting the alternating subtype. Eur J Gastroenterol Hepatol. 2003;15(2): Mertz H, Naliboff B, Mayer EA. Symptoms and physiology in severe chronic constipation. Am J Gastroenterol. 1999;94(1):

5 Mimidis K. Drinking tests in functional dyspepsia: what do they really measure? Neurogastroenterol Motil. 2007;19(12): Owens DM, Nelson DK, Talley NJ.The irritable bowel syndrome: long- term prognosis and the physician- patient interaction. Ann Intern Med. 1995;122(2): Pare P, Ferrazzi S, Thompson WG, Irvine EJ, Rance L. An epidemiological survey of constipation in Canada: definitions, rates, demographics, and predictors of health care seeking. Am J Gastroenterol. 2001;96(11): Passmore AP. Economic aspects of pharmacotherapy for chronic constipation. Pharmacoeconomics. 1995;7(1): Posserud I, Stotzer P- O, Bjornsson E, Abrahamsson H, Simren M. Small- intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut. 2007;56(6): Quigley EM, Vandeplassche L, Kerstens R, Ausma J. Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation a 12- week, randomized, double- blind, placebo- controlled study. Aliment Pharmacol Ther. 2009;29(3): Rao S, Lembo AJ, Shiff SJ, et al. A 12- week, randomized, controlled trial with a 4- week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol 2012;107(11): Rao SS. Constipation: evaluation and treatment. Gastroenterol Clin North Am. 2003;32(2): Read NW. Chapter 91. In: Sleisinger and Fordtran s Gastrointestinal and Liver Disease. 7th ed. Philadelphia, PA:Saunders;2002:1794. Saad RJ, Chey WD. Recent developments in the therapy of irritable bowel syndrome. Expert Opin Investig Drugs. 2008;17(2): Salmon P, Peters S, Stanley I. Patients perceptions of medical explanations for somatisation disorders: qualitative analysis. BMJ. 1999;318: Shepherd SJ, Gibson PR. Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management. J Am Diet Assoc. 2006;106(10): Simren M, Abrahamsson H, Svedlund J, Björnsson ES. Quality of life in patients with irritable bowel syndrome seen in referral centers versus primary care: the impact of gender and predominant bowel pattern. Scand J Gastroenterol. 2001;36(5):

6 Spiegel BM, Gralnek IM, Bolus R, et al. Clinical determinants of health- related quality of life in patients with irritable bowel syndrome. Arch Intern Med. 2004;164(16): Talley NJ, Weaver AL, Zinsmeister AR, Melton LJ. Onset and disappearance of gastrointestinal symptoms and functional gastrointestinal disorders. Am J Epidemiol. 1992;136(2): Talley NJ. Definitions, epidemiology, and impact of chronic constipation. Rev Gastroenterol Disord. 2004;4(Suppl 2):S3- S10. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller- Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(Suppl 2):II43- II47. Tillisch K, Labus JS, Naliboff BD, et al. Characterization of the alternating bowel habit subtype in patients with irritable bowel syndrome. Am J Gastroenterol. 2005;100(4): Wahnschaffe U, Schulzke JD, Zeitz M, Ullrich R. Predictors of clinical response to gluten- free diet in patients diagnosed with diarrhea- predominant irritable bowel syndrome. Clin Gastroenterol Hepatol. 2007;5(7): Wald A. Constipation. Med Clin North Am. 2000;84(5): Wallon C, Yang P- C, Keita AV, et al. Corticotropin- releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro. Gut. 2008;57(1): Van Oudenhove I, Geererts B, Tack J. Limitations of current paradigms for visceral sensitivity testing. Neurogastroenterol Motil. 2008;20(2):95-98.

Alternating bowel pattern: what do people mean?

Alimentary Pharmacology & Therapeutics Alternating bowel pattern: what do people mean? R. S. CHOUNG*, G. R. LOCKE III*, A. R. ZINSMEISTER, L.J.MELTONIIIà &N.J.TALLEY* *Dyspepsia Center and Division of